Studies of herpes simplex virus (HSV) infections in man relate to clinical presentations involving the central nervous system (CNS), infections which do not require brain biopsy, and pharmacologic studies of potential antiviral agents. Physical findings, survival and possible use of idoxuridine in 51 cases of HSV, type 1 encephalitis occurring in North America (1965-1972) and studied by us were correlated. Paralysis and seizures indicate serious diease, but coma dictates a likey fatal outcome. Type-specific IgM and IgG passive hemagglutinating antibodies, conventional, and complement-requiring neutralizing antibodies were studied in human infections and after inoculations in rabbits. A type 2 HSV-variant has been segregated. The occurrence of locally-produced passive hemagglutinating antibodies in spinal fluids after CNS infections is being followed. Cytosine arabinoside was evaluated as a potential antiviral agent, and discarded. The value of idoxuridine is not yet established. In in vitro studies, adenine arabinoside (ara-A) and human leukocyte interferon are clearly synergistic.